Genotype-Tissue Expression (GTEx)

Overview

The Genotype-Tissue Expression (GTEx) project aims to provide to the scientific community a resource with which to study human gene expression and regulation and its relationship to genetic variation. This project will collect and analyze multiple human tissues from donors who are also densely genotyped, to assess genetic variation within their genomes. By analyzing global RNA expression within individual tissues and treating the expression levels of genes as quantitative traits, variations in gene expression that are highly correlated with genetic variation can be identified as expression quantitative trait loci, or eQTLs.

Despite the rapid progress achieved using genome-wide association studies (GWAS; See: http://www.genome.gov/26525384) to identify genetic changes associated with common human diseases, such as heart disease, cancer, diabetes, asthma, and stroke, a large majority of these genetic changes lies outside of the protein-coding regions of genes and often even outside of the genes themselves, making it difficult to discern which genes are affected and by what mechanism. The comprehensive identification of human eQTLs will greatly help to identify genes whose expression is affected by genetic variation, and will provide a valuable basis on which to study the mechanism of that gene regulation.

The GTEx project is a 2-year pilot with the primary goal of testing the feasibility of collecting high-quality RNA and DNA from multiple tissues from approximately 160 donors identified through low post-mortem interval autopsy or organ transplant settings. For a small subset of tissues, collection from living surgery patients will also be performed to compare to the autopsy-derived tissues. If the pilot phase proves successful, the project will be scaled up to involve approximately 1000 donors.

The project will also involve consultation and research into the ethical, legal and social issues raised by the research, support for statistical methods development, and creation of a database to house existing and GTEx-generated eQTL data. The database will allow users to view and download computed eQTL results and provide a controlled access system for de-identified individual-level genotype, expression, and clinical data. The associated tissue repository will also serve as a resource for many additional kinds of analyses.